PTH and PTHR1 in osteocytes. New insights into old partners

doi:10.14310/horm.2002.1730

Cited by 12 publications

(7 citation statements)

References 79 publications

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“…Nevertheless, the mechanism whereby PTH prevents osteocyte apoptosis remains ill-defined. As noted, it was reported that activation of PTH1R in osteocytes could promote gap junction-mediated intercellular coupling, increase expression of MMP-9, and potentiate calcium influx via stretch-activated Ca i 2+ channels, as well as amply the osteogenic response to mechanical loading in vivo, therefore leading to protect osteocytes from apoptosis 135 . Consistent with this notion, it is suggested that G-protein coupled receptors (GPCR) may participate in the cell transduction of mechanical signals, PTH1R and stretch-activated Ca i 2+ channels might both be part of the same mechanosensor system 136 .…”

Section: The Key Molecular Mechanisms In Preserving the Osteocytic VImentioning

confidence: 96%

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

Wang

2020

Cell Death Dis

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Vital osteocytes have been well known to function as an important orchestrator in the preservation of robustness and fidelity of the bone remodeling process. Nevertheless, some key pathological factors, such as sex steroid deficiency and excess glucocorticoids, and so on, are implicated in inducing a bulk of apoptotic osteocytes, subsequently resulting in resorption-related bone loss. As much, osteocyte apoptosis, under homeostatic conditions, is in an optimal state of balance tightly controlled by pro- and anti-apoptotic mechanism pathways. Importantly, there exist many essential signaling proteins in the process of osteocyte apoptosis, which has a crucial role in maintaining a homeostatic environment. While increasing in vitro and in vivo studies have established, in part, key signaling pathways and cross-talk mechanism on osteocyte apoptosis, intrinsic and complex mechanism underlying osteocyte apoptosis occurs in various states of pathologies remains ill-defined. In this review, we discuss not only essential pro- and anti-apoptotic signaling pathways and key biomarkers involved in these key mechanisms under different pathological agents, but also the pivotal role of apoptotic osteocytes in osteoclastogenesis-triggered bone loss, hopefully shedding new light on the attractive and proper actions of pharmacotherapeutics of targeting apoptosis and ensuing resorption-related bone diseases such as osteoporosis and fragility fractures.

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Section: The Key Molecular Mechanisms In Preserving the Osteocytic VImentioning

confidence: 96%

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

Wang

2020

Cell Death Dis

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“…However, when PTH-mediated signaling leads to the phosphorylation and inactivation of SIK2, this allows HDAC4 and HDAC5 to translocate into the nucleus. Within the nucleus, HDAC4 and HDAC5 act to inhibit the function of MEF2C [ 191 ], a transcription factor that normally drives the expression of the Sost gene, which is known to encode a protein that inhibits bone formation. Simultaneously, the inactivated SIK2 reduces the phosphorylation of CREB-regulated transcription coactivator 2 (CRTC2) and leads to its dephosphorylation by an unknown phosphatase, therefore promoting its nuclear translocation.…”

Section: The Direct Interactions Of Pth With Bm Cellsmentioning

confidence: 99%

“…Since SIK2 suppression leads to the regulation of key PTH target genes in osteocytes, not surprisingly, small molecular SIK2 inhibitors such as YKL05099 mimic many of the effects of PTH in osteocytes and following in vivo administration [ 191 ]. Overall, these observations indicate that SIK inhibition is a key signaling mechanism used by PTH to accomplish its physiologic effects in osteocytes.…”

Section: The Direct Interactions Of Pth With Bm Cellsmentioning

confidence: 99%

PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche

Liu,

Rosen

2024

Cells

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Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome being influenced by the manner of PTH administration: continuous or intermittent. In continuous administration, PTH tends to promote bone resorption, possibly by regulating certain genes within bone cells. Conversely, intermittent exposure generally favors bone formation, possibly through transient gene activation. PTH’s role extends to various aspects of bone cell activity. It directly influences skeletal stem cells, osteoblastic lineage cells, osteocytes, and T cells, playing a critical role in bone generation. Simultaneously, it indirectly affects osteoclast precursor cells and osteoclasts, and has a direct impact on T cells, contributing to its role in bone resorption. Despite these insights, the intricate mechanisms through which PTH acts within the bone marrow niche are not entirely understood. This article reviews the dual roles of PTH—catabolic and anabolic—on bone cells, highlighting the cellular and molecular pathways involved in these processes. The complex interplay of these factors in bone remodeling underscores the need for further investigation to fully comprehend PTH’s multifaceted influence on bone health.

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“…PTH subsequently stimulates calcium resorption from bone and bone formation. PTH receptors (PTH1 receptor) are most highly expressed in osteocytes, which are also the most abundant cell type in the bone ( 251 ). Activation of these receptors, which are G-protein coupled, leads to PKA signaling and the CREB-dependent expression of receptor activator of NF-κB ligand (RANKL) ( 252 ) and the MEF2-mediated suppression of sclerostin transcription ( 39 , 253 ); sclerostin is an inhibitor of bone formation.…”

Section: The Physiological Roles Of Salt-inducible Kinasesmentioning

confidence: 99%

The multiple roles of salt-inducible kinases in regulating physiology

Jagannath

Taylor

et al. 2023

Physiological Reviews

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Salt-Inducible kinases, which comprise a family of three homologous serine-threonine kinases were first described for their role in sodium sensing, but have since been shown to regulate multiple aspects of physiology. These kinases are activated or deactivated in response to extracellular signals that are cell surface receptor mediated, and go on to phosphorylate multiple targets including the transcription co-factors CRTC1-3 and the Class IIa histone deacetylases (HDACs). Thus, the SIK family conveys signals about the cellular environment to reprogram transcriptional and post-transcriptional processes in response. In this manner, SIKs have been shown to regulate metabolic responses to feeding/fasting, cell division and oncogenesis, inflammation, and immune responses and most recently, sleep and circadian rhythms. Sleep and circadian rhythms are master regulators of physiology and are exquisitely sensitive to regulation by environmental light, and physiological signals such as need for sleep. Salt-Inducible kinases have been shown to be central the molecular control of both these processes. Here we summarise the molecular mechanisms by which SIKs control these different domains of physiology and highlight where there is mechanistic overlap with sleep/circadian rhythm control.

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PTH and PTHR1 in osteocytes. New insights into old partners

Abstract: ABSTRACT

Cited by 12 publications

References 79 publications

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases

PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche

The multiple roles of salt-inducible kinases in regulating physiology

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